Mutating the side-chains of amino acids in a peptide ligand, with unnatural amino acids, aiming to mitigate its short half-life is an established approach. However, it is hypothesized that mutating specific backbone peptide bonds with bioisosters can be exploited not only to enhance the proteolytic stability of parent peptides, but also to tune its receptor subtype selectivity. Towards this end, four [Y]6-Angiotensin II analogues are synthesized where amide bonds have been replaced by 1,4-disubstituted 1,2,3-triazole isosteres in four different backbone locations. All the analogues possessed enhanced stability in human plasma in comparison with the parent peptide, whereas only two of them achieved enhanced AT2R/AT1R subtype selectivity. This diversification has been studied through 2D NMR spectroscopy and unveiled a putative more structured microenvironment for the two selective ligands accompanied with increased number of NOE cross-peaks. The most potent analogue, compound 2 , has been explored regarding its neurotrophic potential and resulted in an enhanced neurite growth with respect to the established agent C21. 相似文献
In this paper we study the first-order Melnikov function for a planar near-Hamiltonian system near a heteroclinic loop connecting two nilpotent saddles. The asymptotic expansion of this Melnikov function and formulas for the first seven coefficients are given. Next, we consider the bifurcation of limit cycles in a class of hyper-elliptic Hamiltonian systems which has a heteroclinic loop connecting two nilpotent saddles. It is shown that this system can undergo a degenerate Hopf bifurcation and Poincarè bifurcation, which emerges at most four limit cycles in the plane for sufficiently small positive ε. The number of limit cycles which appear near the heteroclinic loop is discussed by using the asymptotic expansion of the first-order Melnikov function. Further more we give all possible distribution of limit cycles bifurcated from the period annulus. 相似文献
The search for the development of a reliable mathematical model for understanding bubble dynamics behavior is an ongoing endeavor.A long list of complex phenomena underlies the physics of this problem.In the past decades,the lattice Boltzmann method has emerged as a promising tool to address such complexities.In this regard,we have applied a 121-velocity multiphase lattice Boltzmann model to an asymmetric cluster of bubbles in an acoustic field.A problem as a benchmark is studied to check the consistency and applicability of the model.The problem of interest is to study the deformation and coalescence phenomena in bubble cluster dynamics,as well as the screening effect on an acoustic multibubble medium.It has been observed that the LB model is able to simulate the combination of the three aforementioned phenomena for a bubble cluster as a whole and for every individual bubble in the cluster. 相似文献
In this paper, the robust finite-time tracking problem is addressed for a square fully actuated class of nonlinear systems subjected to disturbances and uncertainties. Firstly, two applicable lemmas are derived and novel nonlinear sliding surfaces (manifolds) are defined by applying these lemmas. Secondly, by developing the nonsingular terminal sliding mode control, two different types of robust nonlinear control inputs are designed to meet and accomplish the aforementioned finite-time tracking objective. The global finite-time stability of the closed-loop nonlinear system is evaluated analytically and mathematically. The proposed control inputs are utilized to tackle and solve two interesting issues containing (a): the finite-time tracking problem of the unified chaotic system and (b): the finite-time synchronization of two non-identical hyperchaotic systems. Finally, based on MATLAB software, two numerical simulations are carried out to illustrate and demonstrate the effectiveness and performance of the proposed robust finite-time nonlinear control schemes.
The E×B drift instability is studied in Hall thruster using one-dimensional particle in cell(PIC) simulation method.By using the dispersion relation,it is found that unstable modes occur only in discrete bands in k space at cyclotron harmonics.The results indicate that the number of unstable modes increases by increasing the external electric field and decreases by increasing the radial magnetic field.The ion mass does not affect the instability wavelength.Furthermore,the results confirm that there is an instability with short wavelength and high frequency.Finally,it is shown that the electron and ion distribution functions deviate from the initial state and eventually the instability is saturated by ion trapping in the azimuthal direction.Also for light mass ion,the frequency and phase velocity are very high that could lead to high electron mobility in the axial direction. 相似文献
A nanoscale catalyst Fe0(FeNPs) supported on the natrolite zeolite nanoparticles (NANPs) is successfully synthesized and characterized by FT-IR, X-ray diffraction (XRD) and scanning electron microscopy (SEM) and thermogravimetric-differential thermal analysis (TG-DTA). The photodegradation of methyl orange (MO) is studied in aqueous suspension containing the catalyst under UV irradiation and H2O2. The effect of various reaction parameters such as initial dye concentration, irradiation time, pH, H2O2 concentration and catalyst dosage on the decolorization of methyl orange is investigated. The degradation study reveals that the reactivity of the catalysts is in order of: photo-NANPs–FeNPs–H2O2 > photo-NANPs–H2O2 > photo-NANPs–FeNPs > photo-H2O2 > NANPs–FeNPs–H2O2. The results show that methyl orange can be effectively decolorized by NANPs–FeNPs via the pseudo-first-order kinetic model. 相似文献
In this pedagogical communication after demonstrating the legitimacy for using the quantum theory of atoms in molecules (QTAIM) to non-Coulombic systems, Hookean H2+/H32+ species are used for AIM analysis. In these systems, in contrast to their Coulombic counterparts, electron density is atom-like and instead of expected two/three topological atoms, just a single topological atom emerges. This observation is used to demonstrate that what is really “seen” by the topological analysis of electron densities is the clustering of electrons. The very trait of monotonic decay of electron density around the “centers” of clustering guarantees the appearance of topological atoms as basin of attraction of the gradient vector field of the electron density. Although observations with Hookean molecules may seem disappointing at first glance, a careful reasoning points to the fact that the QTAIM methodology is extendable to novel domains, by a knowledge of the morphology of underlying densities, beyond the typical Coulombic systems. 相似文献
N‐(2‐Hydroxypropyl)methacrylamide (HPMA) copolymer‐linked nitroxides were synthesized as macromolecular contrast agents for MR imaging. Molar relaxivities of HPMA copolymer‐linked nitroxides increased linearly in proportion to the number of nitroxides attached per gram of copolymer. HPMA copolymer‐linked nitroxides with 15, 20 and 30 mol‐% nitroxide exhibited higher relaxivities than gadolinium diethylenetriaminepentaacetic acid (Gd‐DTPA). These results demonstrate the potential of HPMA copolymer‐linked nitroxides as MR contrast agents for solid tumors.
Structure of HPMA copolymer‐linked nitroxides. 相似文献